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Get Free AccessThe transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha Chou, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Anna Plym, Ali Sahimi, Thomas J. Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Yamanashi, Yoshinori Murakami, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Masahiko Higashiyama, Akihide Masumoto, Yuji Uchio, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy Pal Choudhury, Johanna Schleutker, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, Christopher T. Rentsch, Kelly Cho, Benjamin H. McMahon, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Røder, Hein Vincent Stroomberg, Jyotsna Batra, Suzanne K. Chambers, Lisa G. Horvath, Judith A. Clements, Wayne D. Tilley, Gail P. Risbridger, Henrik Grönberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordström, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Timothy J. Key, Elio Riboli, Jong Y. Park, Thomas A. Sellers, Hui‐Yi Lin, Demetrius Albanes (2023). Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. , 55(12), DOI: https://doi.org/10.1038/s41588-023-01534-4.
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Type
Article
Year
2023
Authors
92
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1038/s41588-023-01534-4
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